20-37518955-G-A

Position:

• chr20-37518955-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006698.4(BLCAP):​c.220C>T​(p.Pro74Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLCAP NM_006698.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

Genes affected

BLCAP (HGNC:1055): (BLCAP apoptosis inducing factor) This gene encodes a protein that reduces cell growth by stimulating apoptosis. Alternative splicing and the use of alternative promoters result in multiple transcript variants encoding the same protein. This gene is imprinted in brain where different transcript variants are expressed from each parental allele. Transcript variants initiating from the upstream promoter are expressed preferentially from the maternal allele, while transcript variants initiating downstream of the interspersed NNAT gene (GeneID:4826) are expressed from the paternal allele. Transcripts at this locus may also undergo A to I editing, resulting in amino acid changes at three positions in the N-terminus of the protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.190624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLCAP	NM_006698.4	c.220C>T	p.Pro74Ser	missense_variant	2/2	ENST00000373537.7	NP_006689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLCAP	ENST00000373537.7	c.220C>T	p.Pro74Ser	missense_variant	2/2	1	NM_006698.4	ENSP00000362637	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.220C>T (p.P74S) alteration is located in exon 3 (coding exon 1) of the BLCAP gene. This alteration results from a C to T substitution at nucleotide position 220, causing the proline (P) at amino acid position 74 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.058	T;T;T;T;T;T;T;T;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	.;.;.;D;.;.;.;.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.70	D;D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.57	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.40	T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.26	T;.;T;T;T;T;T;.;.
Polyphen		0.0020	B;B;B;B;B;B;B;B;.
Vest4		0.17
MutPred		0.23		Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);Gain of glycosylation at P74 (P = 0.0364);
MVP		0.099
MPC		0.62
ClinPred		0.87	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.046
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-36147357;